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Beta-3 adrenoceptor agonists for the treatment of pulmonary hypertension

a pulmonary hypertension and beta-3 technology, applied in the field of medicine, can solve the problems of lack of ph treatment, high incidence of ph in the population, and high morbidity and mortality, and achieve the effects of reducing pulmonary pressure, favorable response, and beneficial effect of ph

Active Publication Date: 2015-12-31
HOSPITAL CLINIC DE BARCELONA +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention is about finding a way to treat pulmonary hypertension (PH) by stimulating beta-3 adrenergic receptors in the lungs. This approach has shown promising results in reducing pulmonary pressure, increasing oxygen saturation, and reducing pulmonary vascular resistances. Compared to other vasodilators commonly used in this disease, selective beta-3 adrenergic receptor agonists are less likely to cause side effects that can affect the heart and systemic circulation.

Problems solved by technology

The incidence of PH in the population is high and it is associated with high morbidity and mortality.
Currently, there is a lack of treatments for PH.
In addition, these treatments have not proven consistent efficiency in pulmonary hypertension due to a left cardiac pathology (the most frequent), nor in the remaining pulmonary hypertension groups generally.

Method used

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  • Beta-3 adrenoceptor agonists for the treatment of pulmonary hypertension
  • Beta-3 adrenoceptor agonists for the treatment of pulmonary hypertension
  • Beta-3 adrenoceptor agonists for the treatment of pulmonary hypertension

Examples

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examples

Methods

Generating the Experimental Models

Acute PH:

[0087]In 10 2 month old healthy pigs (weighing ≈30 kg) anesthetized, intubated and ventilated with 40% FiO2, while continuously monitoring blood pressure, heart rate (HR), oxygen saturation as well as PAP and repeated measurements of cardiac output (CO) by means of thermodilution using a Swan-Ganz catheter, acute PH was generated by means of pulmonary embolization with a suspension of microspheres (Sephadex G50 coarse; Pharmacia Biotech; Freiburg, Germany) by femoral vein route. The dose necessary for causing an increase of mean PAP≧40 mmHg to remain stable for 10 minutes was administered. At that time the animals were randomized to receive specific β3 agonist BRL37344 (5 μg / Kg) or physiological saline (vehicle).

Chronic PH:

[0088]For the purpose of reproducing a broad spectrum of PH in the general population, 2 experimental models of chronic PH were developed: a pre-capillary model which would represent clinical groups 1, 3, 4 and 5; ...

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Abstract

The invention relates to the use of selective agonists of beta-3 adrenergic receptors for the treatment and / or prevention of pulmonary hypertension.

Description

FIELD OF THE INVENTION[0001]The present invention is comprised within the field of medicine, more particularly, it relates to treating pulmonary hypertension.BACKGROUND OF THE INVENTION[0002]Pulmonary hypertension (PH), defined as the increase of mean pulmonary artery pressure (PAP) above normal values, encompasses a series of diseases characterized by the increase of pulmonary vascular resistances (PVRs) and progressive deterioration of the right ventricle (RV) function (McLaughlin 2009). In this regard, most studies refer to PH for mean PAP values above 25 mmHg, considering that a typical mean PAP in humans is about 12 to 15 mmHg.[0003]There are many causes of PH which have been classified into 5 groups: pulmonary arterial hypertension (PAH); PH due to left heart disease; PH due to lung disease; chronic thromboembolic PH; and PH of an unknown or multifactorial origin. Unlike other groups, PH due to left heart disease is of a post-capillary origin, characterized by the increase of ...

Claims

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Application Information

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IPC IPC(8): A61K31/216A61K31/426
CPCA61K31/195A61K2300/00A61K31/216A61K31/36A61K31/426A61K31/4412A61K31/55A61K31/5517A61K31/63A61P11/00A61P43/00A61P9/00A61P9/12A61K31/135
Inventor IBÁÑEZ CABEZA, BORJAGARCÍA ÁLVAREZ, ANAFUSTER CARULLA, VALENTÍN
Owner HOSPITAL CLINIC DE BARCELONA
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